The noise around statins distracts from its real problems

This month, I co-signed a letter, along with a number of eminent physicians, calling for a full parliamentary investigation into statins. In response, the recipient, Sir Norman Lamb MP, chair of the science and technology committee, wrote to chief medical officer Dame Sally Davies, calling for a review. Our call was based on the lack of clarity on the real benefits of the drug and true incidence of side effects.

In the hands of pharmaceutical industry propagandists, outsider studies have become powerful weapons of misinformation.GPs have no problem using high-dose statins in patients who have already had a heart attack or stroke, as they’re at very high risk of further episodes, and there is some evidence of benefitting that group. Despite this, the data on an individual basis is quite underwhelming.

According to non-transparent industry-sponsored studies taken religiously for five years, heart attack patients can at best expect a one in 83 mortality reduction and a one in 39 chance of preventing a non-fatal heart attack.

But for those who haven’t had a heart attack or stroke, starting a long-term statin brings no mortality benefit.

Prescribing drugs without explaining the absolute risk reduction is both unscientific and unethical. The RCGP is right to raise concerns that this news could lead to people being misdiagnosed and wrongly treated by pharmacists.

Advocates of statins should be treated with scepticism

Statins have many more side-effects than has been admitted, and advocates should be treated with scepticism.

At present, it’s estimated that six to seven million people in the UK take statins. The evidence for the benefit in primary prevention, such as preventing cardiovascular disease in people who don’t have diagnosed cardiovascular disease, is weak.

Most studies, even a large randomised controlled trial like the West of Scotland Coronary Prevention Study showed no impact on overall mortality. True, there was a reduction in incidence rates of strokes and heart attacks, but no one lived longer. Most of the data on statins is presented using a reduction in relative risks, which inflates the benefit. For example, the Heart Protection Study claimed a 40% reduction in mortality from cardiovascular disease, but the reduction in overall mortality was 0.3% per year.

Even if you accept NHS England’s advice, your chance of avoiding a ‘serious vascular event’, such as a heart attack or a stroke, is 140:1 - that is, if you’re healthy with a low risk of cardiovascular disease. On top of this, you have to keep taking the statins for five years.

Because the benefits from a reduction of risk of cardiovascular disease are so small, it becomes crucial to know your chance of suffering side-effects. Of these, myalgia has always been a particular concern. But while the evidence from trials puts this at about 1%, others, especially clinicians who see patients on a daily basis, put side effects at 18%.

This isn’t just unpleasant, it can seriously interfere with the ability to exercise, one of the prime ways of avoiding heart disease. There is also a big debate going on about statins raising the risk of diabetes. The Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial revealed that one in every 100 women taking a statin risked developing type 2 diabetes at 1.9 years.

Now imagine the costs and workload of follow-up appointments and hospital investigations that patients experiencing such side-effects could incur.

With all of these in mind, I urge NHS England to reconsider its position. Instead of converting millions of people into statin users, we should all be focusing on the real factors that reduce the risk of heart disease: healthy diets, exercise and avoiding smoking.

This doesn’t mean that statins should be stopped for patients who are currently taking them and have proven benefits. It’s about statins being used appropriately, in the treatment and secondary prevention of cardiovascular disease.

Dr Chand has put the case against the use of statins, and not for the first time. His main argument seems to be that the beneficial effect of statins are outweighed by the harmful and costly effects. He makes the case that the absolute benefits of statins are small, even if the relative risk benefit seems better. His arguments deserve a response since an intervention must prove that on balance the benefits outweigh the risks of harm, are affordable, and take into account the wishes of the patient. He cites occasional trials without reference, and we are supposed to take his word for it that he has covered the whole literature in a balanced way.
Surely, in order to have a balanced view, all the literature should be considered. Fortunately, we have an independent organisation that does just this already. It is not influenced by ‘pharma’ and has experts and lay people who study the whole body of evidence before making recommendation in Guidelines. It also has Quality Standards (QS) Committees that translate the guidelines into Quality Statements where evidence suggests that recommendations are not being implemented. I have to declare that I have been on some of the guideline groups and quality standards committees. I know the rigour and impartiality that is applied by NICE.

So what does NICE recommend for people who already have known cardiovascular disease? The first priority is for lifestyle change and risk factor management, of course.

QS 100 (2015) draws on many of the NICE guidelines published around CVD prevention. I would urge the reader to consider them all. In summary I draw out the relevant statements.

“Quality statement 6: Statins for secondary prevention: Adults with newly diagnosed cardiovascular disease (CVD) are offered atorvastatin 80 mg.
The rationale is that High-intensity statins are the most clinically effective option for the secondary prevention of CVD – that is, reducing the risk of future CVD events in people who have already had a CVD event, such as a heart attack or stroke. Evidence shows that atorvastatin 80 mg is the most cost-effective high-intensity statin for the secondary prevention of CVD, which can improve clinical outcomes. “
“Quality statement 4: Discussing risks and benefits of statins for primary prevention: Adults with a 10-year risk of cardiovascular disease (CVD) of 10% or more for whom lifestyle changes are ineffective or inappropriate, discuss the risks and benefits of starting statin therapy with their healthcare professional.
The rationale for this is that people who are better informed and involved in decisions about their care are more likely to adhere to their chosen treatment plan, which improves patient experience and clinical outcomes. “
“Quality statement 5: Statins for primary prevention: Adults choosing statin therapy for the primary prevention of cardiovascular disease (CVD) are offered atorvastatin 20 mg.
The rationale here is that High-intensity statins are the most clinically effective treatment option for the primary prevention of CVD – that is, reducing the risk of first CVD events. After a discussion of the risks and benefits of starting statin therapy with a healthcare professional, a person may choose statin therapy as an appropriate treatment to reduce their risk of CVD. When a person decides to have statin therapy, a statin of high intensity and low cost should be offered. Atorvastatin 20 mg is recommended as the preferred initial high-intensity statin to use because it is clinically and cost effective for the primary prevention of CVD. “

One of the key arguments Dr Chand makes is that some trials do not show an all cause mortality benefit. This is true, but they do show reduction in CVD events. They could hardly continue once the Primary Outcomes had been met, until an all cause mortality benefit had been achieved. This would not be ethical.

Of course, no treatment will prevent death in the end. What we desire is to live a healthy life until we die. Living with the disabling effects of a stroke and a failing heart is perhaps to be more dreaded than death. So, preventing these events is a goal in itself, even if (on average) we don’t live longer.

In the end we have to give a balanced view for our patients, given their individual risk of an event or further event. It would be great to extend life, but it is also essential to minimise the risk of disability. The higher risk you are of an event, the greater the likely benefit. For the individual a relative risk reduction is important. Risks of harm and side effects must be considered but should not exclude treatment. Patients must be allowed to decide for themselves and recognise the value of lifestyle change and risk factor optimisation.

Dr Chand's arguments are valid, to an extent. However, there is a danger that his views create a dichotomous view of the benefits and harms of statins. The truth is more nuanced.

Guidelines are not evidence however, you have to look at the evidence behind the guideline, and how strong the evidence is. The guidelines are also carefully worded in that they say that stains are the most effective intervention, and that atorvastatin 80 mg is the most effective statin, but nowhere does it actually say by how much risk is reduced - and don't forget the inflation of apparent risk by making it relative instead of absolute. Re the all cause mortality, and the treatment cohort having fewer strokes and heart attacks, it was pointed out that the statins have saved them from the poor quality of life associated with stroke and heart failure - all well and good, but as the mortality was unchanged , ie the patients overall died at the same expected time, then other causes of death must have gone up, some of them, I would guess also have a poor quality of life, cancer and degenerative neurological disease, to name just 2. I would not take a statin myself for primary prevention, I have to declare that point, but it is a view I have taken from examining the original papers, not the guidelines.

Meddyg | GP Partner/Principal14 Sep 2019 2:37pm
" Re the all cause mortality, and the treatment cohort having fewer strokes and heart attacks, it was pointed out that the statins have saved them from the poor quality of life associated with stroke and heart failure - all well and good, but as the mortality was unchanged"
- should we not treat heart attacks because people would die anyway? well then why not prevent them if we can?

If the net result is the same number of deaths, fewer from heart disease/strokes, more from other causes, AND all the side effects from statins, before we even talk about the cost, both of the drugs and also all the monitoring that goes with it, what is the point? All that money, and all those side effects, just to change the cause of death on a death certificate, but not to change the date?